Yasunobu Okuma and Yasuyuki Nomura
Department of Pharmacology, Graduate School of Pharmaceutical Sciences,
Hokkaido University, Sapporo 060-0812, Japan
Abstract: To elucidate the fundamental mechanism of age-related deficiencies
of learning and to develop effective drugs for intervention in age-related
diseases such as learning dysfunctions, pertinent animal models that have
characteristics closely similar to human dysfunctions should be established.
SAM (senescence-accelerated mouse) has been established as a murine model
of the SAM strains, groups of related inbred strains including nine strains
of accelerated senescence-prone, short-lived mice (SAMP) and three strains
of accelerated senescence-resistant, long-lived mice (SAMR). SAMP-strain
mice show relatively strain-specific age-associated phenotypic pathologies
such as shortened life span and early manifestation of senescence. Among
the SAMP-strain mice, SAMP8 mice show an age-related deterioration in learning
ability. Here, the neuropathological, neurochemical and pharmacological
features of SAM are reported, especially for SAMP8. Moreover, the effects
of several drugs on the biochemical and behavioral alterations in SAMP8
and the etiologic manifestation of accelerated senescence are also discussed.
Keywords: Senescence-accelerated mouse (SAM), Senile dementia, Animal
model, Learning and memory, Aging